HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients
Issued Date
2022-01-01
Resource Type
ISSN
09462716
eISSN
14321440
Scopus ID
2-s2.0-85117052364
Pubmed ID
34651203
Journal Title
Journal of Molecular Medicine
Volume
100
Issue
1
Start Page
101
End Page
113
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Molecular Medicine Vol.100 No.1 (2022) , 101-113
Suggested Citation
Mohanty S., Kamolvit W., Zambrana S., Gonzales E., Tovi J., Brismar K., Östenson C.G., Brauner A. HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients. Journal of Molecular Medicine Vol.100 No.1 (2022) , 101-113. 113. doi:10.1007/s00109-021-02134-7 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83951
Title
HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients
Other Contributor(s)
Abstract
Abstract: Infections are common in patients with diabetes, but increasing antibiotic resistance hampers successful bacterial clearance and calls for alternative treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is known to influence the innate immune defense and could therefore serve as a possible target. However, the impact of high glucose on HIF-1 has received little attention and merits closer investigation. Here, we show that higher levels of proinflammatory cytokines and CAMP, encoding for the antimicrobial peptide cathelicidin, LL-37, correlate with HIF-1 in type 2 diabetic patients. Chemical activation of HIF-1 further enhanced LL-37, IL-1β, and IL-8 in human uroepithelial cells exposed to high glucose. Moreover, HIF-1 activation of transurethrally infected diabetic mice resulted in lower bacterial load. Drugs activating HIF-1 could therefore in the future potentially have a therapeutic role in clearing bacteria in diabetic patients with infections where antibiotic treatment failed. Key messages: • Mohanty et al. “HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients.” • Our study highlights induction of the antimicrobial peptide, LL-37, and strengthening of the innate immunity through hypoxia-inducible factor 1 (HIF-1) in diabetes. • Our key observations are: 1. HIF-1 activation increased LL-37 expression in human urothelial cells treated with high glucose. In line with that, we demonstrated that patients with type 2 diabetes living at high altitude had increased levels of the LL-37. 2. HIF-1 activation increased IL-1β and IL-8 in human uroepithelial cells treated with high glucose concentration. 3. Pharmacological activation of HIF-1 decreased bacterial load in the urinary bladder of mice with hereditary diabetes. • We conclude that enhancing HIF-1 may along with antibiotics in the future contribute to the treatment in selected patient groups where traditional therapy is not possible.